Procedures for total joint replacement have revolutionized the treatment of patients with end-stage destructive arthritis. Although improvements in biomaterials and surgical techniques have yielded excellent clinical results, long-term followup studies reveal an alarming rate of prosthetic loosening that ultimately requires revision surgery. Despite numerous studies describing the tissue reaction associated with orthopedic implants, very little is known regarding the specific cellular and biochemical events that determine the characteristics of the histologic and connective tissue response to these materials. The goal of this proposal is to develope an in vitro cell culture model employing bone and other connective tissue cells to study the effects of orthopaedic implant biomaterials on the expression of differentiated cell function. Biochemical and molecular mechanisms regulating general cellular activities such as attachment, proliferation, cytoskeletal organization and matrix biosynthesis will be investigated and comparative results obtained in different cell types will help establish the specificity of the observations made with bone cells. In addition this model will be used to explore experimental approaches for modulating the phenotypic expression of bone and other connective tissue cells grown on implant materials. A suitable in vitro model for studying the specific biologic processes involved in the interaction between orthopedic biomaterials and connective tissue cells should be useful in developing improved techniques and biomaterials for total joint replacement.